Use of atorvastatin to inhibit hypoxia-induced myocardin expression

Chiung Zuan Chiu, Bao Wei Wang, Kou Gi Shyu

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background Hypoxia induces the formation of reactive oxygen species (ROS), myocardin expression and cardiomyocyte hypertrophy. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been demonstrated to have both antioxidant and antihypertrophic effects. We evaluated the pathways of atorvastatin in repressing ROS and myocardin after hypoxia to prevent cardiomyocyte hypertrophy. Materials and methods Cultured rat neonatal cardiomyocytes were subjected to hypoxia, and the expression of myocardin and ROS were evaluated. Different signal transduction inhibitors, atorvastatin and N-acetylcysteine (NAC) were used to identify the pathways that inhibited myocardin expression and ROS. Electrophoretic motility shift assay (EMSA) and luciferase assay were used to identify the binding of myocardin/serum response factor (SRF) and transcription to cardiomyocytes. Cardiomyocyte hypertrophy was assessed by 3H-proline incorporation assay. Results Myocardin expression after hypoxia was inhibited by atorvastatin, RhoA/Rho kinase inhibitor (Y27632), extracellular signal-regulated kinase (ERK) small interfering RNA (siRNA)/ERK pathway inhibitor (PD98059), myocardin siRNA and NAC. Bindings of myocardin/SRF, transcription of myocardin/SRF to cardiomyocytes, presence of myocardin in the nuclei of cardiomyocytes and protein synthesis after hypoxia were identified by EMSA, luciferase assay, confocal microscopy and 3H-proline assay and were suppressed by atorvastatin, Y27632, PD98059 and NAC. Conclusions Hypoxia in neonatal cardiomyocytes increases myocardin expression and ROS to cause cardiomyocyte hypertrophy, which can be prevented by atorvastatin by suppressing ROS and myocardin expression.

Original languageEnglish
Pages (from-to)564-571
Number of pages8
JournalEuropean Journal of Clinical Investigation
Volume42
Issue number5
DOIs
Publication statusPublished - May 2012

Fingerprint

Cardiac Myocytes
Assays
Reactive Oxygen Species
Serum Response Factor
Hypertrophy
Acetylcysteine
Extracellular Signal-Regulated MAP Kinases
Transcription
Luciferases
Proline
Small Interfering RNA
Atorvastatin Calcium
Hypoxia
myocardin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
rho-Associated Kinases
Signal transduction
Confocal microscopy
Confocal Microscopy
Rats

Keywords

  • Cardiomyocyte hypertrophy
  • Reactive oxygen species
  • Statins
  • Transcription

ASJC Scopus subject areas

  • Medicine(all)
  • Clinical Biochemistry
  • Biochemistry

Cite this

Use of atorvastatin to inhibit hypoxia-induced myocardin expression. / Chiu, Chiung Zuan; Wang, Bao Wei; Shyu, Kou Gi.

In: European Journal of Clinical Investigation, Vol. 42, No. 5, 05.2012, p. 564-571.

Research output: Contribution to journalArticle

Chiu, Chiung Zuan ; Wang, Bao Wei ; Shyu, Kou Gi. / Use of atorvastatin to inhibit hypoxia-induced myocardin expression. In: European Journal of Clinical Investigation. 2012 ; Vol. 42, No. 5. pp. 564-571.
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N2 - Background Hypoxia induces the formation of reactive oxygen species (ROS), myocardin expression and cardiomyocyte hypertrophy. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been demonstrated to have both antioxidant and antihypertrophic effects. We evaluated the pathways of atorvastatin in repressing ROS and myocardin after hypoxia to prevent cardiomyocyte hypertrophy. Materials and methods Cultured rat neonatal cardiomyocytes were subjected to hypoxia, and the expression of myocardin and ROS were evaluated. Different signal transduction inhibitors, atorvastatin and N-acetylcysteine (NAC) were used to identify the pathways that inhibited myocardin expression and ROS. Electrophoretic motility shift assay (EMSA) and luciferase assay were used to identify the binding of myocardin/serum response factor (SRF) and transcription to cardiomyocytes. Cardiomyocyte hypertrophy was assessed by 3H-proline incorporation assay. Results Myocardin expression after hypoxia was inhibited by atorvastatin, RhoA/Rho kinase inhibitor (Y27632), extracellular signal-regulated kinase (ERK) small interfering RNA (siRNA)/ERK pathway inhibitor (PD98059), myocardin siRNA and NAC. Bindings of myocardin/SRF, transcription of myocardin/SRF to cardiomyocytes, presence of myocardin in the nuclei of cardiomyocytes and protein synthesis after hypoxia were identified by EMSA, luciferase assay, confocal microscopy and 3H-proline assay and were suppressed by atorvastatin, Y27632, PD98059 and NAC. Conclusions Hypoxia in neonatal cardiomyocytes increases myocardin expression and ROS to cause cardiomyocyte hypertrophy, which can be prevented by atorvastatin by suppressing ROS and myocardin expression.

AB - Background Hypoxia induces the formation of reactive oxygen species (ROS), myocardin expression and cardiomyocyte hypertrophy. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been demonstrated to have both antioxidant and antihypertrophic effects. We evaluated the pathways of atorvastatin in repressing ROS and myocardin after hypoxia to prevent cardiomyocyte hypertrophy. Materials and methods Cultured rat neonatal cardiomyocytes were subjected to hypoxia, and the expression of myocardin and ROS were evaluated. Different signal transduction inhibitors, atorvastatin and N-acetylcysteine (NAC) were used to identify the pathways that inhibited myocardin expression and ROS. Electrophoretic motility shift assay (EMSA) and luciferase assay were used to identify the binding of myocardin/serum response factor (SRF) and transcription to cardiomyocytes. Cardiomyocyte hypertrophy was assessed by 3H-proline incorporation assay. Results Myocardin expression after hypoxia was inhibited by atorvastatin, RhoA/Rho kinase inhibitor (Y27632), extracellular signal-regulated kinase (ERK) small interfering RNA (siRNA)/ERK pathway inhibitor (PD98059), myocardin siRNA and NAC. Bindings of myocardin/SRF, transcription of myocardin/SRF to cardiomyocytes, presence of myocardin in the nuclei of cardiomyocytes and protein synthesis after hypoxia were identified by EMSA, luciferase assay, confocal microscopy and 3H-proline assay and were suppressed by atorvastatin, Y27632, PD98059 and NAC. Conclusions Hypoxia in neonatal cardiomyocytes increases myocardin expression and ROS to cause cardiomyocyte hypertrophy, which can be prevented by atorvastatin by suppressing ROS and myocardin expression.

KW - Cardiomyocyte hypertrophy

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